Tacrolimus with mycophenotate mofetil or sirolimus compared with calcineurin inhibitor-free immunosuppression (sirolimus/mycophenolate mofetil) after heart transplantation: 5-year results
Tacrolimus with mycophenotate mofetil or sirolimus compared with calcineurin inhibitor-free immunosuppression (sirolimus/mycophenolate mofetil) after heart transplantation: 5-year results
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DOI：
10.1016/j.healun.2012.11.028
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发表时间：
2013-03-01
影响因子：
8.9
通讯作者：
Meiser, Bruno
中科院分区：
文献类型：
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作者：
Kaczmarek, Ingo;Zaruba, Marc-Michael;Meiser, Bruno
背景：尽管免疫抑制疗法有所改进，但对于心脏移植受者来说，最有利的组合尚未确定。方法：2003-2005年间，78例心脏移植受者随机分为激素+他克莫司+霉酚酸酯(TAC/MMF；n=34)、TAC+西罗莫司(TAC/SRL；n=29)、SRL+MMF(SRL/MMF)+抗胸腺细胞球蛋白(ATG；n=15)。结果：TAC/MMF、TAC/SRL和SRL/MMF的5年生存率分别为85.3%、93.1%和86.7%(TAC/MMF与TAC/SIR、TAC/MMF与SIR/MMF、TAC/SIR与SIR/MMF的P=0.86)。尽管使用了ATG，SRL/MMF组患者的急性排斥反应发生率较低：SRL/MMF组，82.4%；TAC/SRL组，85.2%；SRL/MMF组，73.3%(p=0.33)。与TAC/MMF组相比，5年后SRL/MMF组的肾功能得到了保护(p=0.045)：TAc/MMF1.70+/-0.91 mg/dl；TAc/Srl：1.44+/-0.65 mg/dl；SRU/MMF组心脏移植物血管病变发生率(93.3%)明显高于TAC/MMF组(73.5%)和TAC/SRL组(80.8%)，差异无统计学意义。未发生巨细胞病毒感染的TAC/MMF为72.2%，TAC/SRL为89.7%，SRL/MMF为86.7%。TAC/SRL与TAC/MMF相比，对巨细胞病毒感染的抵抗力有提高的趋势(p=0.076)。在基于sRL的免疫抑制方案中，更频繁的研究药物中断(tac/srl vs tac/mmf，p=0.034；srl/mmf vs.tac/mmf，p=0.003)。结论：这3种方案在5年内没有产生生存优势，在无钙化抑制剂的组中，排斥反应和不良反应的数字发生率更高。在无钙调神经磷酸酶抑制剂的手臂中，观察到了一种有利于心脏移植物血管病变和肾功能保护的趋势。然而，对结果的临床相关性尚不清楚，因为只有少数患者接受了指定的治疗方案。J心肺移植2013；32：277-284(C)2013国际心肺移植学会。版权所有。
BACKGROUND: Despite improvements in immunosuppressive therapy, the most advantageous combination for cardiac transplant recipients has not been established. This randomized controlled trial was performed to evaluate the efficacy and safety of 3 immunosuppressive protocols.METHODS: Between 2003 and 2005, 78 de novo cardiac transplant recipients were randomized 2:2:1 to receive steroids and tacrolimus plus mycophenolate mofetil (TAC/MMF; n = 34), TAC and sirolimus (TAC/SRL; n = 29), or SRL and MMF (SRL/MMF) plus anti-thymocyte globulin (ATG; n = 15). Steroids were withdrawn after 6 months.RESULTS: The 5-year survival was 85.3% for TAC/MMF, 93.1% for TAC/SRL, and 86.7% for SRL/MMF (p = 0.31 for TAC/MMF vs TAC/SIR; p = 0.47 for TAC/MMF vs SIR/MMF and p = 0.86 for TAC/SIR vs SIR/MMF). Despite the use of ATG, patients in the SRL/MMF group revealed numerically fewer freedom from acute rejection episodes: SRL/MMF, 82.4%; TAC/SRL, 85.2%; SRL/MMF, 73.3% (p = 0.33). Mean creatinine at 5 years revealed preservation of renal function in the SRL/MMF vs the TAC/MMF group (p = 0.045): TAC/MMF, 1.70 +/- 0.91 mg/dl; TAC/SRL, 1.44 +/- 0.65 mg/dl; and SRL/MM:F, 1.25 +/- 0.46 mg/dl. Freedom from cardiac allograft vasculopathy was improved in the SRU/MMF group (93.3%) compared with TAC/MMF (73.5%) and TAC/SRL (80.8%) groups, reaching no statistical significance. Freedom from cytomegalovirus infection was TAC/MMF, 72.2%; TAC/SRL, 89.7%; and SRL/MMF, 86.7%. There was a trend toward improved freedom from cytomegalovirus infection with TAC/SRL vs TAC/MMF (p = 0.076). More frequent discontinuations of study medication occurred in SRL-based immunosuppression protocols (TAC/SRL vs TAC/MMF, p = 0.034; SRL/MMF vs TAC/MMF, p = 0.003).CONCLUSIONS: The 3 strategies yield no survival advantage at 5 years, with higher numeric rates of rejection and adverse effects in the calcinemin inhibitor-free arm. A trend was observed in favor of freedom from cardiac allograft vasculopathy and preservation of renal function in the calcineurin inhibitor-free arm. However, the clinical relevance on outcomes is unclear because only few patients were receiving the assigned treatment protocols. J Heart Lung Transplant 2013;32:277-284 (C) 2013 International Society for Heart and Lung Transplantation. All rights reserved.